This project will continue to analyze the genetic basis of the response of rats to major transplantation antigens. Populations of T cells highly selected for reactivity to transplantation antigens in vitro will be analysed functionally, and work will begin on characterising their receptor using both the cells themselves and also somatic cell hybrids, derived from them. The nature of the very powerful immune response genes which govern rat responses to alloantigens will be investigated in detail, particularly with reference to their locus of action and to the origin of their specificity. The specificity of cytotoxic killer cells is also modulated by genetic factors in the responder: the properties of these variations in specificity will be analysed using genetic methods coupled with identification of the fine specificity using inhibition of lysis by monoclonal alloantibodies. The antigenic structure of major alloantigens in the rat will be investigated using monoclonal antibody probes.